The working hypothesis underlying this study is that destruction of tumor cells could be induced by a cell-mediated immunologic response directed not against tumor specific antigens (TSA), but against (i) antigenic determinants of antibodies which combine with TSA, or (ii) distinct antigenic determinants of tissue components located primarily within tumor foci. The requirement for the first model is the availability of anti-TSA antibodies in significant quantities. Inbred mice and rats are being immunized according to different protocols with the syngeneic virus- induced tumors, Po and PW13, and strain 13 guinea pigs with MC-D tumor. The isolation of anti-TSA antibodies by absorption onto tumor cells and subsequent elution will be attempted. Conjugates of these antibodies with tyrosine azobenzene arsonate TABA will be injected into tumor bearing hosts and subsequently lymphoid cells from syngeneic animals sensitized to TABA will be administered, in the expectation that these cells will home onto tumor foci coated with anti- TSA antibodies conjugated to TABA and thus unleash a local cytotoxic reaction. For the second model, it is anticipated that tumors growing within a fibrin lattice ( e.g. MC-D sarcoma) would be destroyed by a two-step immunologically specific strategy consisting of (a) injection of the tumor bearing host with heterologous antibodies directed against the unique determinants of fibrin (which have been localized within tumor foci) and (b) administration of lymphoid cells from syngeneic animals sensitized to a state of cell-mediated hypersensitivity against immunoglobulins isotypic with anti-fibrin antibodies. Preliminary results supporting pigs receiving rabbit anti-fibrin antibodies and lymphoid cells from syngeneic guinea pigs sensitized to rabbit immunoglobulins. In a third study it is proposed to establish if lymphoblast-like cells, emerging from an in vitro culture of the MC-D tumor, retain their cytotoxic potential on administration into synegeneic guinea pigs bearing this tumor.